Antiretroviral treatment for mothers started during pregnancy and continued throughout the breastfeeding period resulted in a significantly lower rate of mother-to-child HIV transmission when compared with the standard short-course regimen, investigators on the Kesho Bora study reported this week at the Fifth International AIDS Society conference in Cape Town.
The Kesho Bora study, conducted in Kenya, South Africa and Burkina Faso, found that antiretroviral treatment for the mother with a protease inhibitor-based regimen was significantly more effective than short-course treatment in which the mother took AZT from week 28 to 36 of pregnancy with AZT/3TC and single dose nevirapine at the onset of labour, and AZT/3TC for one week, while the infant received single dose nevirapine with one week of AZT/3TC, and was either formula fed or breastfed with weaning at 6 months.
The differing short-course regimens studied reflect variations in practice as a result of previous clinical trial results.
In the Kesho Bora study 824 pregnant women not currently eligible for antiretroviral treatment for their own health, with CD4 counts between 200 and 500 cells/mm3, were randomised to one of two regimens.
Women in the triple therapy group (n=413) received AZT/3TC and lopinavir/ritonavir (Kaletra) from the third trimester of pregnancy until six months postpartum, the point at which breastfeeding was recommended to cease.
Women in the short-course group received AZT (zidovudine) from week 28 to 36 of pregnancy until the onset of labour, when they received AZT/3TC and single dose nevirapine. They continued to take AZT/3TC for one week after delivery, an amendment introduced to the study in December 2007.
All infants received single dose nevirapine within 72 hours of delivery, and one week of AZT treatment was added from December 2007.
Women were counselled on the risk of transmission through breastfeeding and offered the choice of free formula for bottle feeding, or exclusive breastfeeding with weaning over a two-week period commencing at five and a half months. During the study 76 and 78% of mothers in the two study arms breastfed at some point, with around 45% in each arm breastfeeding exclusively during the first three months after delivery. The average duration of breastfeeding was 21 weeks.
Study recruitment began in June 2005 and the study was fully recruited by August 2008, with the result that the majority of births in the study occurred in the period before the December 2007 protocol amendment.
In the triple ART arm there were 402 live births, and infant HIV infections as measured by real-time PCR were detected in 1.8% at birth, 3.3% at six weeks, 4.9% at six months and 5.5% at one year. The reduction in the risk of transmission at one year was 42% when compared to the short-course regimen. A log rank test at 12 months showed this difference to be statistically significant (p = 0.039).
In comparison there were 411 live births in the short-course arm, and infant HIV infections were detected in 2.2% at birth, 4.8% at six weeks, 8.5% at six months and 9.5% at one year.
A difference in infant survival became apparent after six months: 6.3% of infants born to mothers in the triple therapy arm had died after 12 months of follow-up, compared to 10% of infants in the short-course arm, a reduction in risk of 37%. However a log rank test at 12 months did not show this difference to be statistically significant (p = 0.086).
Subgroup analysis showed that the reduction in HIV infection rate associated with the triple therapy regimen was statistically significant only in the group of mothers with baseline CD4 counts between 200 and 350 cells/mm3. In the infants born to these mothers there was a cumulative HIV infection rate of 5.5% by six months in the triple ART group and 10.5% in the short-course group, rising to 6.1 and 11.1% at 12 months (p = 0.044).
A significant difference was not detected in infants born to mothers with baseline CD4 counts between 350 and 500 cells/mm3, and there was no significant difference in HIV infections according to regimen in the infants of mothers who ever breastfed during the study (5.9% vs 10.2%, p = 0.064).
The study authors note that the biggest effect of triple ART was detected between six weeks and six months after delivery, and in mothers with CD4 counts between 200 and 350 cells/mm3, reinforcing the view that if earlier treatment is to be recommended in resource-limited settings, this group should be a priority. The median CD4 count in this study population was 335 cells/mm3.
The authors also noted that a small number of postnatal transmissions occurred after six months, the point at which breastfeeding was recommended to stop, indicating the importance of continuing ART until breastfeeding stops completely.
Analyses of adherence and the long-term impact of treatment on maternal health will take place, and full results of the study, with 12-month and 18-month follow-up on all participants, are expected in 2010.